Chitosan Synthese
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Chitosan is a linear
polysaccharide Polysaccharides (), or polycarbohydrates, are the most abundant carbohydrates found in food. They are long-chain polymeric carbohydrates composed of monosaccharide units bound together by glycosidic linkages. This carbohydrate can react with wat ...
composed of randomly distributed β-(1→4)-linked D-glucosamine (deacetylated unit) and ''N''-acetyl-D-glucosamine (acetylated unit). It is made by treating the
chitin Chitin (carbon, C8hydrogen, H13oxygen, O5nitrogen, N)n ( ) is a long-chain polymer of N-Acetylglucosamine, ''N''-acetylglucosamine, an amide derivative of glucose. Chitin is the second most abundant polysaccharide in nature (behind only cell ...
shells of shrimp and other crustaceans with an alkaline substance, such as
sodium hydroxide Sodium hydroxide, also known as lye and caustic soda, is an inorganic compound with the formula . It is a white solid ionic compound consisting of sodium cations and hydroxide anions . Sodium hydroxide is a highly corrosive base (chemistry), ...
. Chitosan has a number of commercial and possible biomedical uses. It can be used in
agriculture Agriculture encompasses crop and livestock production, aquaculture, and forestry for food and non-food products. Agriculture was a key factor in the rise of sedentary human civilization, whereby farming of domesticated species created ...
as a seed treatment and
biopesticide A biopesticide is a biological substance or organism that damages, kills, or repels organisms seens as pests. Biological pest management intervention involves predatory, parasitic, or chemical relationships. They are obtained from organisms incl ...
, helping plants to fight off fungal infections. In
winemaking Winemaking, wine-making, or vinification is the production of wine, starting with the selection of the fruit, its Ethanol fermentation, fermentation into alcohol, and the bottling of the finished liquid. The history of wine-making stretches over ...
, it can be used as a fining agent, also helping to prevent spoilage. In industry, it can be used in a self-healing
polyurethane Polyurethane (; often abbreviated PUR and PU) is a class of polymers composed of organic chemistry, organic units joined by carbamate (urethane) links. In contrast to other common polymers such as polyethylene and polystyrene, polyurethane term ...
paint Paint is a material or mixture that, when applied to a solid material and allowed to dry, adds a film-like layer. As art, this is used to create an image or images known as a painting. Paint can be made in many colors and types. Most paints are ...
coating. In
medicine Medicine is the science and Praxis (process), practice of caring for patients, managing the Medical diagnosis, diagnosis, prognosis, Preventive medicine, prevention, therapy, treatment, Palliative care, palliation of their injury or disease, ...
, it is useful in bandages to reduce bleeding and as an antibacterial agent; it can also be used to help deliver drugs through the skin.


History

In 1799, British chemist
Charles Hatchett Charles Hatchett Fellow of the Royal Society, FRS FRSE (2 January 1765 – 10 March 1847) was an English mineralogist and analytical chemist who discovered the element niobium, for which he proposed the name "columbium". Hatchett was elected a ...
experimented with decalcifying the shells of various crustaceans, finding that a soft, yellow and cartilage-like substance was left behind that we now know to be chitin. In 1859, French physiologist
Charles Marie Benjamin Rouget Charles Marie Benjamin Rouget (19 August 1824 – 1904, Paris) was a French physiologist born in Gisors, Gisors, Eure. He studied at the Collège Sainte-Barbe with medical training at hospitals in Paris. He was later a professor of physiology ...
found that boiling chitin in potassium hydroxide solution could deacetylate it to produce a substance that was soluble in dilute organic acids, that he called ''chitine modifiée''. In 1894, German chemist
Felix Hoppe-Seyler Ernst Felix Immanuel Hoppe-Seyler (''né'' Felix Hoppe; 26 December 1825 – 10 August 1895) was a German physiologist and chemist, and the principal founder of the disciplines of biochemistry and molecular biology. He had discovered Yeast nuclei ...
named the substance chitosan. From 1894 to 1930 there was a period of debate and confusion over the exact composition of chitin and particularly whether animal and fungal forms were the same chemicals. In 1930 the first chitosan films and fibres were patented but competition from petroleum-derived polymers limited their uptake. It was not until the 1970s that there was renewed interest in the compound, spurred partly by laws that prevented the dumping of untreated shellfish waste.


Manufacture

Chitosan is produced commercially by
deacetylation : In chemistry, acetylation is an organic esterification reaction with acetic acid. It introduces an acetyl group into a chemical compound. Such compounds are termed ''acetate esters'' or simply ''acetates''. Deacetylation is the opposite react ...
of
chitin Chitin (carbon, C8hydrogen, H13oxygen, O5nitrogen, N)n ( ) is a long-chain polymer of N-Acetylglucosamine, ''N''-acetylglucosamine, an amide derivative of glucose. Chitin is the second most abundant polysaccharide in nature (behind only cell ...
, which is the structural element in the
exoskeleton An exoskeleton () . is a skeleton that is on the exterior of an animal in the form of hardened integument, which both supports the body's shape and protects the internal organs, in contrast to an internal endoskeleton (e.g. human skeleton, that ...
of
crustaceans Crustaceans (from Latin meaning: "those with shells" or "crusted ones") are invertebrate animals that constitute one group of Arthropod, arthropods that are traditionally a part of the subphylum Crustacea (), a large, diverse group of mainly aquat ...
(such as crabs and shrimp) and cell walls of
fungi A fungus (: fungi , , , or ; or funguses) is any member of the group of eukaryotic organisms that includes microorganisms such as yeasts and mold (fungus), molds, as well as the more familiar mushrooms. These organisms are classified as one ...
. A common method for obtaining chitosan is the deacetylation of chitin using sodium hydroxide in excess as a reagent and water as a solvent. The reaction follows first-order kinetics though it occurs in two steps; the
activation energy In the Arrhenius model of reaction rates, activation energy is the minimum amount of energy that must be available to reactants for a chemical reaction to occur. The activation energy (''E''a) of a reaction is measured in kilojoules per mole (k ...
barrier for the first stage is estimated at 48.8 kJ·mol−1 at and is higher than the barrier to the second stage. The degree of deacetylation (%) can be determined by
NMR spectroscopy Nuclear magnetic resonance spectroscopy, most commonly known as NMR spectroscopy or magnetic resonance spectroscopy (MRS), is a spectroscopic technique based on re-orientation of atomic nuclei with non-zero nuclear spins in an external magnetic f ...
and the degree of deacetylation in commercially available chitosan ranges from 60 to 100%. On average, the molecular weight of commercially produced chitosan is 3800–20,000  daltons. Nanofibrils have been made using chitin and chitosan.


Chemical modifications

Chitosan contains the following three functional groups: C2- NH2, C3- OH, and C6-OH. C3-OH has a large spatial site resistance and therefore is relatively difficult to modify. C2-NH2 is highly reactive for fine modifications and is the most common modifying group in chitosan.Qin, Y.; Li, P.; Guo, Z. Cationic chitosan derivatives as potential antifungals: A review of structural optimization and applications. Carbohydr. Polym. 2020, 236, 116002. In chitosan, although amino groups are more prone to nucleophilic reactions than hydroxyl groups, both can react non-selectively with electrophilic reagents such as acids, chlorides, and
haloalkanes The haloalkanes (also known as halogenoalkanes or alkyl halides) are alkanes containing one or more halogen substituents of hydrogen atom. They are a subset of the general class of halocarbons, although the distinction is not often made. Haloalka ...
to functionalize them.Sahariah, P.; Masson, M. Antimicrobial chitosan and chitosan derivatives: A review of the structure–activity relationship. Biomacromolecules 2017, 18, 3846–3868. Since chitosan contains a variety of functional groups, it can be functionalized in different ways such as phosphorylation, thiolation, and quaternization to adapt it to specific purposes.


Phosphorylated chitosan

Water-soluble phosphorylated chitosan can be obtained by the reaction of
phosphorus pentoxide Phosphorus pentoxide is a chemical compound with molecular formula Phosphorus, P4Oxygen, O10 (with its common name derived from its empirical formula, P2O5). This white crystalline solid is the anhydride of phosphoric acid. It is a powerful desic ...
and chitosan under low-temperature conditions using methane sulfonic acid as the catalyst; phosphorylated chitosan with good antibacterial activity and ionic properties can be prepared by graft copolymerization of chitosan monophosphate.Jayakumar, R.; Selvamurugan, N.; Nair, S.k.V.; Tokura, S.; Tamura, H. Preparative methods of phosphorylated chitin and chitosan—An overview. Int. J. Biol. Macromol. 2008, 43, 221–225.Ardean, C.; Davidescu, C.M.; Nemeş, N.S.; Negrea, A.; Ciopec, M.; Duteanu, N.; Negrea, P.; Duda-Seiman, D.; Musta, V. Factors influencing the antibacterial activity of chitosan and chitosan modified by functionalization. Int. J. Mol. Sci. 2021, 22, 7449. The good water solubility and metal chelating properties of
phosphorylated In biochemistry, phosphorylation is described as the "transfer of a phosphate group" from a donor to an acceptor. A common phosphorylating agent (phosphate donor) is ATP and a common family of acceptor are alcohols: : This equation can be writt ...
chitosan and its derivatives make them widely used in
tissue engineering Tissue engineering is a biomedical engineering discipline that uses a combination of cells, engineering, materials methods, and suitable biochemical and physicochemical factors to restore, maintain, improve, or replace different types of biolo ...
, drug delivery carriers, tissue regeneration, and the food industry.Liu, L.; Miao, Y.; Shi, X.; Gao, H.; Wang, Y. Phosphorylated Chitosan Hydrogels Inducing Osteogenic Differentiation of Osteoblasts via JNK and p38 Signaling Pathways. ACS Biomater. Sci. Eng. 2020, 6, 1500–1509.Wei, J.; Xue, W.; Yu, X.; Qiu, X.; Liu, Z. pH Sensitive phosphorylated chitosan hydrogel as vaccine delivery system for intramuscular immunization. J. Biomater. Appl. 2017, 31, 1358–1369.Han, G.; Liu, S.; Pan, Z.; Lin, Y.; Ding, S.; Li, L.; Luo, B.; Jiao, Y.; Zhou, C. Sulfonated chitosan and phosphorylated chitosan coated polylactide membrane by polydopamine-assisting for the growth and osteogenic differentiation of MC3T3-E1s. Carbohydr. Polym. 2020, 229, 115517. In tissue engineering, phosphorylated chitosan exhibits improved swelling and ionic conductivity. Although its
crystallinity Crystallinity refers to the degree of structural order in a solid. In a crystal, the atoms or molecules are arranged in a regular, periodic manner. The degree of crystallinity has a large influence on hardness, density, transparency and diffusi ...
is reduced, its
tensile strength Ultimate tensile strength (also called UTS, tensile strength, TS, ultimate strength or F_\text in notation) is the maximum stress that a material can withstand while being stretched or pulled before breaking. In brittle materials, the ultimate ...
remains largely unchanged. These properties make it useful for creating scaffolds that can support bone tissue regeneration by binding growth factors and promoting stem cell differentiation into bone-forming cells.Muzzarelli, R.A. Chitosan composites with inorganics, morphogenetic proteins and stem cells, for bone regeneration. Carbohydr. Polym. 2011, 83, 1433–1445. Additionally, to enhance the solubility of chitosan-based
hydrogels A hydrogel is a biphasic material, a mixture of porous and permeable solids and at least 10% of water or other interstitial fluid. The solid phase is a water insoluble three dimensional network of polymers, having absorbed a large amount of ...
at neutral or alkaline pH, the derivative ''N''-methylene phosphonic acid chitosan (NMPC-GLU) has been developed. This material maintains good
mechanical strength Mechanical may refer to: Machine * Machine (mechanical), a system of mechanisms that shape the actuator input to achieve a specific application of output forces and movement * Mechanical calculator, a device used to perform the basic operations of ...
and improve
cell proliferation Cell proliferation is the process by which ''a cell grows and divides to produce two daughter cells''. Cell proliferation leads to an exponential increase in cell number and is therefore a rapid mechanism of tissue growth. Cell proliferation ...
, making it valuable for biomedical applications.LogithKumar, R.; KeshavNarayan, A.; Dhivya, S.; Chawla, A.; Saravanan, S.; Selvamurugan, N. A review of chitosan and its derivatives in bone tissue engineering. Carbohydr. Polym. 2016, 151, 172–188.


Thiolated chitosan

Thiolated chitosan is produced by attaching thiol groups to the amino groups of chitosan using a thiol-containing coupling agent.Bernkop-Schnürch, A.; Hornof, M.; Guggi, D. Thiolated chitosans. Eur. J. Pharm. Biopharm. 2004, 57, 9–17.Liu, X.; Li, X.; Zhang, R.; Wang, L.; Feng, Q. A novel dual microsphere based on water-soluble thiolated chitosan/mesoporous calcium carbonate for controlled dual drug delivery. Mater. Lett. 2021, 285, 129142. The primary site for this modification is the amino group at the 2nd position of chitosan's glucosamine units. During this process, thioglycolic acid and cysteine mediate the reaction, forming an amide bond between the thiol group and chitosan. At a pH below 5, thiol activity is reduced, which limits disulfide bond formation. The modified chitosan exhibits improved adhesive properties and stability due to the covalent attachment of the thiol groups. Lower pH reduces oxidation, enhancing its adhesion properties.Mueller, C.; Verroken, A.; Iqbal, J.; Bernkop-Schnuerch, A. Thiolated chitosans: In vitro comparison of mucoadhesive properties. J. Appl. Polym. Sci. 2012, 124, 5046–5055.Laffleur, F. Evaluation of chemical modified hydrogel formulation for topical suitability. Int. J. Biol. Macromol. 2017, 105, 1310–1314.Federer, C.; Kurpiers, M.; Bernkop-Schnurch, A. Thiolated chitosans: A multi-talented class of polymers for various applications. Biomacromolecules 2020, 22, 24–56. Additionally, thiolated chitosan can interact with cell membrane receptors, improving membrane permeabilityZhang, Y.; Zhou, S.; Deng, F.; Chen, X.; Wang, X.; Wang, Y.; Zhang, H.; Dai, W.; He, B.; Zhang, Q. The function and mechanism of preactivated thiomers in triggering epithelial tight junctions opening. Eur. J. Pharm. Biopharm. 2018, 133, 188–199. and showing potential for applications in bacterial adhesion prevention, for example for coating stainless steel.Mirani, Z.A.; Fatima, A.; Urooj, S.; Aziz, M.; Khan, M.N.; Abbas, T. Relationship of cell surface hydrophobicity with biofilm formation and growth rate: A study on Pseudomonas aeruginosa, Staphylococcus aureus, and Escherichia coli. Iran. J. Basic Med. Sci. 2018, 21, 760.Xu, L.Q.; Pranantyo, D.; Neoh, K.-G.; Kang, E.-T.; Fu, G.D. Thiol reactive maleimido-containing tannic acid for the bioinspired surface anchoring and post-functionalization of antifouling coatings. ACS Sustain. Chem. Eng. 2016, 4, 4264–4272.


Ionic chitosan

There are two main methods of chitosan quaternization: direct quaternization and indirect quaternization. * The direct quaternization of chitosan amino acids treats chitosan with
haloalkanes The haloalkanes (also known as halogenoalkanes or alkyl halides) are alkanes containing one or more halogen substituents of hydrogen atom. They are a subset of the general class of halocarbons, although the distinction is not often made. Haloalka ...
under alkaline conditions. Another method is the reaction of chitosan with
aldehydes In organic chemistry, an aldehyde () (lat. ''al''cohol ''dehyd''rogenatum, dehydrogenated alcohol) is an organic compound containing a functional group with the structure . The functional group itself (without the "R" side chain) can be referred ...
first, followed by reduction, and finally with haloalkanes to obtain quaternized chitosan.Wei, L.; Tan, W.; Wang, G.; Li, Q.; Dong, F.; Guo, Z. The antioxidant and antifungal activity of chitosan derivatives bearing Schiff bases and quaternary ammonium salts. Carbohydr. Polym. 2019, 226, 115256.Liu, W.; Qin, Y.; Liu, S.; Xing, R.; Yu, H.; Chen, X.; Li, K.; Li, P. Synthesis, characterization and antifungal efficacy of chitosan derivatives with triple quaternary ammonium groups. Int. J. Biol. Macromol. 2018, 114, 942–949. * The indirect quaternization method refers to introducing small molecules containing quaternary ammonium groups into chitosan, such as glycidyl trimethyl ammonium chloride, (5-bromopentyl) trimethyl ammonium bromide, etc.Shagdarova, B.; Lunkov, A.; Il′ina, A.; Varlamov, V. Investigation of the properties of N- 2-hydroxy-3-trimethylammonium) propylchloride chitosan derivatives. Int. J. Biol. Macromol. 2019, 124, 994–1001.De Oliveira Pedro, R.; Schmitt, C.C.; Neumann, M.G. Syntheses and characterization of amphiphilic quaternary ammonium chitosan derivatives. Carbohydr. Polym. 2016, 147, 97–103. Quaternary ammonium groups can further be introduced into the chitosan backbone via azide-alkyne cycloaddition,Tan, W.; Zhang, J.; Mi, Y.; Dong, F.; Li, Q.; Guo, Z. Synthesis, characterization, and evaluation of antifungal and antioxidant properties of cationic chitosan derivative via azide-alkyne click reaction. Int. J. Biol. Macromol. 2018, 120, 318–324. or by dissolving chitosan in alkali and
urea Urea, also called carbamide (because it is a diamide of carbonic acid), is an organic compound with chemical formula . This amide has two Amine, amino groups (–) joined by a carbonyl functional group (–C(=O)–). It is thus the simplest am ...
and then reacting it with 3-chloro-2-hydroxypropyl trimethylammonium chloride,Song, H.; Wu, H.; Li, S.; Tian, H.; Li, Y.; Wang, J. Homogeneous synthesis of cationic chitosan via new avenue. Molecules 2018, 23, 1921. which provides a simple and
green Green is the color between cyan and yellow on the visible spectrum. It is evoked by light which has a dominant wavelength of roughly 495570 nm. In subtractive color systems, used in painting and color printing, it is created by a com ...
solution to achieve chitosan functionalization. Cationic derivatives of chitosan have important roles in bioadhesion, absorption enhancement, anti-inflammatory, antibacterial and anti-tumor applications. Chitosan modified with quaternary ammonium groups is one of the most common cationic chitosan derivatives. Quaternized chitosan with a permanent positive charge has increased antimicrobial activity and solubility compared to normal chitosan.Mi, Y.; Tan, W.; Zhang, J.; Wei, L.; Chen, Y.; Li, Q.; Dong, F.; Guo, Z. Synthesis, characterization, and antifungal property of hydroxypropyltrimethyl ammonium chitosan halogenated acetates. Mar. Drugs 2018, 16, 315.


Properties

Chitosan commonly dissolves via three methods—acidic solutions, ionic liquids, or aqueous CO₂. The
amino In chemistry, amines (, ) are organic compounds that contain carbon-nitrogen bonds. Amines are formed when one or more hydrogen atoms in ammonia are replaced by alkyl or aryl groups. The nitrogen atom in an amine possesses a lone pair of elec ...
group in chitosan has a p''K''b value of ~6.5, which leads to significant protonation in neutral solution, increasing with increased acidity (decreased pH) and the %DA-value. This makes chitosan water-soluble and a bioadhesive which readily binds to negatively charged surfaces such as mucosal membranes. Also, chitosan can effectively bind to other surface via hydrophobic interaction and/or cation-π interaction (chitosan as a cation source) in aqueous solution. The free amine groups on chitosan chains can make
crosslinked In chemistry and biology, a cross-link is a bond or a short sequence of bonds that links one polymer chain to another. These links may take the form of covalent bonds or ionic bonds and the polymers can be either synthetic polymers or natural ...
polymeric networks with
dicarboxylic acid In organic chemistry, a dicarboxylic acid is an organic compound containing two carboxyl groups (). The general molecular formula for dicarboxylic acids can be written as , where R can be aliphatic or aromatic.Boy Cornils, Peter Lappe "Dicarbox ...
s to improve chitosan's mechanical properties. Chitosan enhances the transport of polar
drugs A drug is any chemical substance other than a nutrient or an essential dietary ingredient, which, when administered to a living organism, produces a biological effect. Consumption of drugs can be via inhalation, injection, smoking, ingestio ...
across epithelial surfaces, and is biocompatible and
biodegradable Biodegradation is the breakdown of organic matter by microorganisms, such as bacteria and fungi. It is generally assumed to be a natural process, which differentiates it from composting. Composting is a human-driven process in which biodegrada ...
. However, it is not approved by the FDA for drug delivery. Purified quantities of chitosan are available for
biomedical Biomedicine (also referred to as Western medicine, mainstream medicine or conventional medicine)
applications.


Physicochemical properties

Chitosan has biological properties, such as
biodegradability and
biocompatibility Biocompatibility is related to the behavior of biomaterials in various contexts. The term refers to the ability of a material to perform with an appropriate host response in a specific situation. The ambiguity of the term reflects the ongoin ...
.Islam, S.; Bhuiyan, M.R.; Islam, M. Chitin and chitosan: Structure, properties and applications in biomedical engineering. J. Polym. Environ. 2017, 25, 854–866. The biological properties of chitosan are closely related to its physicochemical structure, which includes the degree of deacetylation, water content, and molecular weight. Deacetylation refers to the process of removing the acetyl group from chitosan, and this process determines the content of free amine groups in chitosan. Studies have shown that chitosan has good solubility only when the degree of deacetylation is above 85%. The enhanced chitosan uptake is mainly due to the interaction of positively charged chitosan with cell membranes, activation of chlorine–bicarbonate exchange channels, and reorganization of proteins associated with epithelial tight junctions, thus opening epithelial tight junctions.Vllasaliu, D.; Casettari, L.; Fowler, R.; Exposito-Harris, R.; Garnett, M.; Illum, L.; Stolnik, S. Absorption-promoting effects of chitosan in airway and intestinal cell lines: A comparative study. Int. J. Pharm. 2012, 430, 151–160. Chitosan inhibits the growth of different bacteria and fungi by mechanisms involving several factors, including the degree of deacetylation, pH, divalent cations, and solvent type.


Uses


Agricultural and horticultural use

The agricultural and horticultural uses for chitosan, primarily for plant defense and yield increase, are based on how this glucosamine polymer influences the biochemistry and molecular biology of the plant cell. The cellular targets are the plasma membrane and nuclear chromatin. Subsequent changes occur in cell membranes, chromatin, DNA, calcium, MAP kinase, oxidative burst, reactive oxygen species, callose pathogenesis-related (PR) genes, and phytoalexins. Chitosan was first registered as an active ingredient (licensed for sale) in 1986.


Natural biocontrol and elicitor

In
agriculture Agriculture encompasses crop and livestock production, aquaculture, and forestry for food and non-food products. Agriculture was a key factor in the rise of sedentary human civilization, whereby farming of domesticated species created ...
, chitosan is typically used as a natural seed treatment and plant growth enhancer, and as an ecologically friendly
biopesticide A biopesticide is a biological substance or organism that damages, kills, or repels organisms seens as pests. Biological pest management intervention involves predatory, parasitic, or chemical relationships. They are obtained from organisms incl ...
substance that boosts the innate ability of plants to defend themselves against fungal infections. Degraded molecules of chitin/chitosan exist in soil and water. Chitosan applications for plants and crops are regulated in the USA by the Environmental Protection Agency, and the USDA
National Organic Program The National Organic Program (NOP) is the federal regulatory framework in the United States, United States of America governing organic food. It is also the name of the United States Department of Agriculture (USDA) Agricultural Marketing Service ...
regulates its use on organic certified farms and crops. EPA-approved, biodegradable chitosan products are allowed for use outdoors and indoors on plants and crops grown commercially and by consumers. In the European Union and United Kingdom, chitosan is registered as a "basic substance" for use as a biological
fungicide Fungicides are pesticides used to kill parasitic fungi or their spores. Fungi can cause serious damage in agriculture, resulting in losses of yield and quality. Fungicides are used both in agriculture and to fight fungal infections in animals, ...
and
bactericide A bactericide or bacteriocide, sometimes abbreviated Bcidal, is a substance which kills bacteria. Bactericides are disinfectants, antiseptics, or antibiotics. However, material surfaces can also have bactericidal properties based solely on their p ...
on a wide range of crops. The natural biocontrol ability of chitosan should not be confused with the effects of fertilizers or pesticides upon plants or the environment. Chitosan active biopesticides represent a new tier of cost-effective biological control of crops for agriculture and horticulture. The biocontrol mode of action of chitosan elicits natural innate defense responses within plant to resist insects, pathogens, and soil-borne diseases when applied to foliage or the soil. Chitosan increases photosynthesis, promotes and enhances plant growth, stimulates nutrient uptake, increases germination and sprouting, and boosts plant vigor. When used as a seed treatment or seed coating on cotton, corn, seed potatoes, soybeans, sugar beets, tomatoes, wheat, and many other seeds, it elicits an
innate immunity The innate immune system or nonspecific immune system is one of the two main immunity strategies in vertebrates (the other being the adaptive immune system). The innate immune system is an alternate defense strategy and is the dominant immune s ...
response in developing roots which destroys parasitic cyst nematodes without harming beneficial
nematodes The nematodes ( or ; ; ), roundworms or eelworms constitute the phylum Nematoda. Species in the phylum inhabit a broad range of environments. Most species are free-living, feeding on microorganisms, but many are parasitic. Parasitic worms (he ...
and organisms. Agricultural applications of chitosan can reduce environmental stress due to drought and soil deficiencies, strengthen seed vitality, improve stand quality, increase yields, and reduce fruit decay of vegetables, fruits and citrus crops . Horticultural application of chitosan increases blooms and extends the life of cut flowers and Christmas trees. The
US Forest Service The United States Forest Service (USFS) is an agency within the U.S. Department of Agriculture. It administers the nation's 154 national forests and 20 national grasslands covering of land. The major divisions of the agency are the Chief's ...
has conducted research on chitosan to control pathogens in pine trees and increase resin pitch outflow which resists pine beetle infestation. Chitosan has been studied for applications in agriculture and horticulture dating back to the 1980s. By 1989, chitosan salt solutions were applied to crops for improved freeze protection or to crop seed for seed priming. Shortly thereafter, chitosan salt received the first ever
biopesticide A biopesticide is a biological substance or organism that damages, kills, or repels organisms seens as pests. Biological pest management intervention involves predatory, parasitic, or chemical relationships. They are obtained from organisms incl ...
label from the EPA, then followed by other
intellectual property Intellectual property (IP) is a category of property that includes intangible creations of the human intellect. There are many types of intellectual property, and some countries recognize more than others. The best-known types are patents, co ...
applications. Chitosan has been used to protect plants in space, as well, exemplified by
NASA The National Aeronautics and Space Administration (NASA ) is an independent agencies of the United States government, independent agency of the federal government of the United States, US federal government responsible for the United States ...
's experiment to protect adzuki beans grown aboard the space shuttle and
Mir ''Mir'' (, ; ) was a space station operated in low Earth orbit from 1986 to 2001, first by the Soviet Union and later by the Russia, Russian Federation. ''Mir'' was the first modular space station and was assembled in orbit from 1986 to ...
space station in 1997. NASA results revealed chitosan induces increased growth (biomass) and pathogen resistance due to elevated levels of β-(1→3)-glucanase enzymes within plant cells. NASA confirmed chitosan elicits the same effect in plants on earth. In 2008, the EPA approved natural broad-spectrum elicitor status for an ultralow molecular active ingredient of 0.25% chitosan. A natural chitosan elicitor solution for agriculture and horticultural uses was granted an amended label for foliar and irrigation applications by the EPA in 2009. Given its low potential for toxicity and abundance in the natural environment, chitosan does not harm people, pets, wildlife, or the environment when used according to label directions. Chitosan blends do not work against
bark beetle A bark beetle is the common name for the subfamily of beetles Scolytinae. Previously, this was considered a distinct family (Scolytidae), but is now understood to be a specialized clade of the "true weevil" family (Curculionidae). Although th ...
s when put on a tree's leaves or in its soil.


Filtration

Chitosan can be used in
hydrology Hydrology () is the scientific study of the movement, distribution, and management of water on Earth and other planets, including the water cycle, water resources, and drainage basin sustainability. A practitioner of hydrology is called a hydro ...
as a part of a
filtration Filtration is a physical separation process that separates solid matter and fluid from a mixture using a ''filter medium'' that has a complex structure through which only the fluid can pass. Solid particles that cannot pass through the filte ...
process. Chitosan causes the fine sediment particles to bind together, and is subsequently removed with the sediment during sand filtration. It also removes heavy minerals,
dye Juan de Guillebon, better known by his stage name DyE, is a French musician. He is known for the music video of the single "Fantasy Fantasy is a genre of speculative fiction that involves supernatural or Magic (supernatural), magical ele ...
s, and oils from the water. As an additive in water filtration, chitosan combined with sand filtration removes up to 99% of
turbidity Turbidity is the cloudiness or haziness of a fluid caused by large numbers of individual particles that are generally invisible to the naked eye, similar to smoke in air. The measurement of turbidity is a key test of both water clarity and wa ...
. Chitosan is among the biological adsorbents used for heavy metals removal without negative environmental impacts. In combination with
bentonite Bentonite ( ) is an Absorption (chemistry), absorbent swelling clay consisting mostly of montmorillonite (a type of smectite) which can either be Na-montmorillonite or Ca-montmorillonite. Na-montmorillonite has a considerably greater swelli ...
,
gelatin Gelatin or gelatine () is a translucent, colorless, flavorless food ingredient, commonly derived from collagen taken from animal body parts. It is brittle when dry and rubbery when moist. It may also be referred to as hydrolyzed collagen, coll ...
,
silica gel Silica gel is an amorphous and porosity, porous form of silicon dioxide (silica), consisting of an irregular three-dimensional framework of alternating silicon and oxygen atoms with nanometer-scale voids and pores. The voids may contain wate ...
,
isinglass Isinglass ( ) is a form of collagen obtained from the dried swim bladders of fish. The English word origin is from the obsolete Dutch ''huizenblaas'' – ''huizen'' is a kind of sturgeon, and ''blaas'' is a bladder, or German ''Hausenblase'', ...
, or other fining agents, it is used to
clarify Clarification, clarifications, or clarify may refer to: * Clarification (cooking), purification of broths * Clarification, preparation of clarified butter * Clarification and stabilization of wine In winemaking, clarification and stabilization ...
wine Wine is an alcoholic drink made from Fermentation in winemaking, fermented fruit. Yeast in winemaking, Yeast consumes the sugar in the fruit and converts it to ethanol and carbon dioxide, releasing heat in the process. Wine is most often made f ...
,
mead Mead (), also called honey wine, and hydromel (particularly when low in alcohol content), is an alcoholic beverage made by fermenting honey mixed with water, and sometimes with added ingredients such as fruits, spices, grains, or hops. The alco ...
, and
beer Beer is an alcoholic beverage produced by the brewing and fermentation of starches from cereal grain—most commonly malted barley, although wheat, maize (corn), rice, and oats are also used. The grain is mashed to convert starch in the ...
. Added late in the brewing process, chitosan improves
flocculation In colloidal chemistry, flocculation is a process by which colloidal particles come out of Suspension (chemistry), suspension to sediment in the form of floc or flake, either spontaneously or due to the addition of a clarifying agent. The actio ...
, and removes yeast cells, fruit particles, and other detritus that cause hazy wine.


Winemaking and fungal source chitosan

Chitosan has a long history for use as a fining agent in winemaking. Fungal source chitosan has shown an increase in settling activity, reduction of oxidized polyphenolics in juice and wine, chelation and removal of copper (post-racking) and control of the spoilage
yeast Yeasts are eukaryotic, single-celled microorganisms classified as members of the fungus kingdom (biology), kingdom. The first yeast originated hundreds of millions of years ago, and at least 1,500 species are currently recognized. They are est ...
'' Brettanomyces''. These products and uses are approved for European use by the EU and OIV standards.


Wound management

Chitosan-based wound dressings have been widely explored for a variety of acute and chronic wounds. Chitosan has the ability to adhere to
fibrinogen Fibrinogen (coagulation factor I) is a glycoprotein protein complex, complex, produced in the liver, that circulates in the blood of all vertebrates. During tissue and vascular injury, it is converted Enzyme, enzymatically by thrombin to fibrin ...
, which produces increased
platelet Platelets or thrombocytes () are a part of blood whose function (along with the coagulation#Coagulation factors, coagulation factors) is to react to bleeding from blood vessel injury by clumping to form a thrombus, blood clot. Platelets have no ...
adhesion, causing clotting of blood and hemostasis. Chitosan hemostatic agents are salts made from mixing chitosan with an organic acid (such as succinic or lactic acid). Chitosan may have other properties conducive to wound healing, including antibacterial and antifungal activity, which remain under preliminary research. Chitosan is used within some wound dressings to decrease bleeding. Upon contact with blood, the bandage becomes sticky, effectively sealing the laceration. Chitosan hydrogel-based wound dressings have also been found useful as burn dressings, and for the treatment of chronic diabetic wounds and hydrofluoric acid burns. Chitosan-containing wound dressings received approval for medical use in the United States in 2003.


Temperature-sensitive hydrogels

Chitosan is dissolved in dilute organic acid solutions but is insoluble in high concentrations of hydrogen ions at pH 6.5 and is precipitated as a gel-like compound. Chitosan is positively charged by amine groups, making it suitable for binding to negatively charged molecules. However, it has disadvantages such as low mechanical strength and low-temperature response rate; it must be combined with other gelling agents to improve its properties. Using glycerolphosphate salts (possessing a single anionic head) without chemical modification or cross-linking, the pH-dependent gelation properties can be converted to temperature-sensitive gelation properties. In the year 2000, Chenite was the first to design the temperature-sensitive chitosan hydrogels drug delivery system using chitosan and β-glycerol phosphate. This new system can remain in the liquid state at room temperature, while becoming gel with increasing temperature above the physiological temperature (37 °C). Phosphate salts cause a particular behaviour in chitosan solutions, thereby allowing these solutions to remain soluble in the physiological pH range (pH 7), and they will be gel only at body temperature. When the liquid solution of chitosan-glycerol phosphate, containing the drug, enters the body through a syringe injection, it becomes a water-insoluble gel at 37 °C. The entrapped drug particles between the hydrogel chains will be gradually released.


Research

Chitosan and derivatives have been developed for their potential use in nanomaterials,
bioadhesive Bioadhesives are natural polymeric materials that act as adhesives Adhesive, also known as glue, cement, mucilage, or paste, is any non-metallic substance applied to one or both surfaces of two separate items that binds them together and resis ...
s, wound dressing materials,
drug delivery Drug delivery involves various methods and technologies designed to transport pharmaceutical compounds to their target sites helping therapeutic effect. It involves principles related to drug preparation, route of administration, site-specif ...
systems, enteric coatings, and in
medical device A medical device is any device intended to be used for medical purposes. Significant potential for hazards are inherent when using a device for medical purposes and thus medical devices must be proved safe and effective with reasonable assura ...
s. For example, chitosan nanoparticles produced using sodium tripolyphosphate as crosslinker are stable and biocompatible enough to be used as drug delivery materials.


Bioprinting

Bioinspired
materials A material is a substance or mixture of substances that constitutes an object. Materials can be pure or impure, living or non-living matter. Materials can be classified on the basis of their physical and chemical properties, or on their ge ...
, a manufacturing concept inspired by natural
nacre Nacre ( , ), also known as mother-of-pearl, is an organicinorganic composite material produced by some molluscs as an inner shell layer. It is also the material of which pearls are composed. It is strong, resilient, and iridescent. Nacre is ...
,
shrimp A shrimp (: shrimp (American English, US) or shrimps (British English, UK)) is a crustacean with an elongated body and a primarily Aquatic locomotion, swimming mode of locomotion – typically Decapods belonging to the Caridea or Dendrobranchi ...
carapace A carapace is a dorsal (upper) section of the exoskeleton or shell in a number of animal groups, including arthropods, such as crustaceans and arachnids, as well as vertebrates, such as turtles and tortoises. In turtles and tortoises, the unde ...
, or insect
cuticle A cuticle (), or cuticula, is any of a variety of tough but flexible, non-mineral outer coverings of an organism, or parts of an organism, that provide protection. Various types of "cuticle" are non- homologous, differing in their origin, structu ...
s, has led to development of bioprinting methods to manufacture large scale consumer objects using chitosan. This method is based on replicating the molecular arrangement of chitosan from natural materials into fabrication methods, such as
injection molding Injection moulding (U.S. spelling: injection molding) is a manufacturing process for producing parts by injecting molten material into a mould, or mold. Injection moulding can be performed with a host of materials mainly including metals (for ...
or mold casting. Once discarded, chitosan-constructed objects are
biodegradable Biodegradation is the breakdown of organic matter by microorganisms, such as bacteria and fungi. It is generally assumed to be a natural process, which differentiates it from composting. Composting is a human-driven process in which biodegrada ...
and non-
toxic Toxicity is the degree to which a chemical substance or a particular mixture of substances can damage an organism. Toxicity can refer to the effect on a whole organism, such as an animal, bacterium, or plant, as well as the effect on a subst ...
. The method is used to engineer and bioprint human organs or tissues.
Pigment A pigment is a powder used to add or alter color or change visual appearance. Pigments are completely or nearly solubility, insoluble and reactivity (chemistry), chemically unreactive in water or another medium; in contrast, dyes are colored sub ...
ed chitosan objects can be recycled, with the option of reintroducing or discarding the dye at each recycling step, enabling reuse of the polymer independently of colorants. Unlike other plant-based
bioplastic Bioplastics are plastic materials produced from renewable biomass sources. Timeline of plastic development, Historically, bioplastics made from natural materials like shellac or Celluloid, cellulose had been the first plastics. Since the end of ...
s (e.g.
cellulose Cellulose is an organic compound with the chemical formula, formula , a polysaccharide consisting of a linear chain of several hundred to many thousands of glycosidic bond, β(1→4) linked glucose, D-glucose units. Cellulose is an important s ...
,
starch Starch or amylum is a polymeric carbohydrate consisting of numerous glucose units joined by glycosidic bonds. This polysaccharide is produced by most green plants for energy storage. Worldwide, it is the most common carbohydrate in human diet ...
), the main natural sources of chitosan come from marine environments and do not compete for land or other human resources. 3D bioprinting of
tissue engineering Tissue engineering is a biomedical engineering discipline that uses a combination of cells, engineering, materials methods, and suitable biochemical and physicochemical factors to restore, maintain, improve, or replace different types of biolo ...
scaffolds for creating artificial tissues and organs is another application where chitosan has gained popularity. Chitosan has high
biocompatibility Biocompatibility is related to the behavior of biomaterials in various contexts. The term refers to the ability of a material to perform with an appropriate host response in a specific situation. The ambiguity of the term reflects the ongoin ...
, biodegradability, and
antimicrobial An antimicrobial is an agent that kills microorganisms (microbicide) or stops their growth (bacteriostatic agent). Antimicrobial medicines can be grouped according to the microorganisms they are used to treat. For example, antibiotics are used aga ...
, hemostatic,
wound healing Wound healing refers to a living organism's replacement of destroyed or damaged tissue by newly produced tissue. In undamaged skin, the epidermis (surface, epithelial layer) and dermis (deeper, connective layer) form a protective barrier again ...
and immunomodulatory activities which make it suitable for making artificial tissues.


Weight loss

Chitosan is marketed in a tablet form as a "fat binder". Although the effect of chitosan on lowering
cholesterol Cholesterol is the principal sterol of all higher animals, distributed in body Tissue (biology), tissues, especially the brain and spinal cord, and in Animal fat, animal fats and oils. Cholesterol is biosynthesis, biosynthesized by all anima ...
and body weight has been evaluated, the effect appears to have no or low clinical importance. Reviews from 2016 and 2008 found there was no significant effect, and no justification for overweight people to use chitosan supplements. In 2015, the U.S.
Food and Drug Administration The United States Food and Drug Administration (FDA or US FDA) is a List of United States federal agencies, federal agency of the United States Department of Health and Human Services, Department of Health and Human Services. The FDA is respo ...
issued a public advisory about supplement retailers who made exaggerated claims concerning the supposed weight loss benefit of various products.


Biodegradable antimicrobial food packaging

Microbial contamination of food products accelerates the deterioration process and increases the risk of foodborne illness caused by potentially life-threatening pathogens. Ordinarily, food contamination originates superficially, requiring surface treatment and packaging as crucial factors to assure food quality and safety. Biodegradable chitosan films have potential for preserving various food products, retaining their firmness and restricting weight loss due to dehydration. In addition, composite biodegradable films containing chitosan and antimicrobial agents are in development as safe alternatives to preserve food products.


Battery electrolyte

Chitosan is being investigated as an
electrolyte An electrolyte is a substance that conducts electricity through the movement of ions, but not through the movement of electrons. This includes most soluble Salt (chemistry), salts, acids, and Base (chemistry), bases, dissolved in a polar solven ...
for
rechargeable batteries A rechargeable battery, storage battery, or secondary cell (formally a type of energy accumulator), is a type of electrical battery which can be charged, discharged into a load, and recharged many times, as opposed to a disposable or prima ...
with good performance and low
environmental impact Environmental issues are disruptions in the usual function of ecosystems. Further, these issues can be caused by humans ( human impact on the environment) or they can be natural. These issues are considered serious when the ecosystem cannot reco ...
due to rapid biodegradability, leaving recycleable zinc. The electrolyte has excellent physical stability up to 50 °C, electrochemical stability up to 2 V with zinc electrodes, and accommodates
redox reaction Redox ( , , reduction–oxidation or oxidation–reduction) is a type of chemical reaction in which the oxidation states of the reactants change. Oxidation is the loss of electrons or an increase in the oxidation state, while reduction is ...
s involved in the Zn-MnO2 alkaline system. results were promising, but the battery needed testing on a larger scale and under actual use conditions.


References


External links

* International research projec
Nano3Bio
focused on tailor-made biotechnological production of chitosans (funded by the European Union) {{Authority control Antihemorrhagics Biopesticides Elicitors Polysaccharides